Acesso às vias aéreas guiado por ultrassom

Ultrasound has increasingly growing applications in anesthesia. This procedure has proven to be a novel, non‐invasive and simple technique for the upper airway management, proving to be a useful tool, not only in the operating room but also in the intensive care unit and emergency department. Indeed, over the years mounting evidence has showed an increasing role of ultrasound in airway management. In this review, the authors will discuss the importance of ultrasound in the airway preoperative assessment as a way of detecting signs of difficult intubation or to define the type and/or size of the endotracheal tube as well as to help airway procedures such as endotracheal intubation, cricothyrotomy, percutaneous tracheal intubation, retrograde intubation as well as the criteria for extubation.     

Differences in cortisol concentrations in adolescents with eating disorders: a systematic review

Objective

To perform a systematic review of the literature for scientific evidence of possible differences in cortisol concentrations in adolescents with eating disorders.

Lemierre's syndrome

Lemierre's syndrome (LS) is an uncommon but potentially life-threatening complication of an anaerobic oropharyngeal infection, affecting young adults and adolescents. The disease is characterised by a septic thrombophlebitis of the internal jugular vein and "metastatic" infections, which can be followed by fulminant sepsis and rapid death. More recently, it has been reported a recrudescence of this condition, which could be attributable to alterations in antibiotic usage patterns. The authors report the case of a LS secondary to a bout of intense cough, a cause not yet described in the literature, highlighting the importance of a quick diagnosis and the institution of an appropriate therapy.     

Molecular genetics approaches in yeast to study amyloid diseases

The occurrence of protein aggregates in ordered fibrillar structures known as amyloid, found inside and outside of brain cells, is a feature shared by many neurodegenerative disorders, including Alzheimer's, Parkinson's, and Huntington's diseases. Although the molecular mechanisms that underlie neurodegeneration will ultimately have to be tested in neuronal and animal models, there are several distinct advantages in using model organisms to elucidate fundamental aspects of protein aggregation, amyloid formation, and toxicity. Here, we review recent studies indicating that amyloid formation by disease-causing proteins can be faithfully recapitulated in simple yeast-based models in Saccharomyces cerevisiae. These studies have already contributed to our basic understanding of molecular chaperone function/dysfunction in Huntington's disease, and functional genomics approaches being undertaken currently will likely bear novel insights into the genes and pathways that modulate neuronal cell dysfunction and death in these devastating diseases. A final advantage of using yeast to study amyloid formation and toxicity is the ease and rapidity with which large-scale drug-screening efforts can be conducted in this model organism.     

Simple fluorescent PCR method for detection of large deletions in the beta-globin gene cluster

We developed a semi-automated approach to detect large deletions in the beta-globin gene cluster, based on the quantitative differences in the amplifications of samples by a fluorescent PCR. With this strategy, we were able to detect the presence of HPFH-2 in an African-Brazilian subject, confirmed by sequencing analysis. Differently from other PCR strategies, GAP-PCR for example, it has the potential to identify new deletions.     

α-Synuclein phosphorylation at serine 129 occurs after initial protein deposition and inhibits seeded fibril formation and toxicity

α-Synuclein (α-syn) phosphorylation at serine 129 (pS129–α-syn) is substantially increased in Lewy body disease, such as Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). However, the pathogenic relevance of pS129–α-syn remains controversial, so we sought to identify when pS129 modification occurs during α-syn aggregation and its role in initiation, progression and cellular toxicity of disease. Using diverse aggregation assays, including real-time quaking-induced conversion (RT-QuIC) on brain homogenates from PD and DLB cases, we demonstrated that pS129–α-syn inhibits α-syn fibril formation and seeded aggregation. We also identified lower seeding propensity of pS129–α-syn in cultured cells and correspondingly attenuated cellular toxicity. To build upon these findings, we developed a monoclonal antibody (4B1) specifically recognizing nonphosphorylated S129–α-syn (WT–α-syn) and noted that S129 residue is more efficiently phosphorylated when the protein is aggregated. Using this antibody, we characterized the time-course of α-syn phosphorylation in organotypic mouse hippocampal cultures and mice injected with α-syn preformed fibrils, and we observed aggregation of nonphosphorylated α-syn followed by later pS129–α-syn. Furthermore, in postmortem brain tissue from PD and DLB patients, we observed an inverse relationship between relative abundance of nonphosphorylated α-syn and disease duration. These findings suggest that pS129–α-syn occurs subsequent to initial protein aggregation and apparently inhibits further aggregation. This could possibly imply a potential protective role for pS129–α-syn, which has major implications for understanding the pathobiology of Lewy body disease and the continued use of reduced pS129–α-syn as a measure of efficacy in clinical trials.

Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are both associated with underlying Lewy body disease, which represents the second most common neurodegenerative disorder after Alzheimer’s disease (1, 2). The neuropathological hallmark of Lewy body disease is the intracellular aggregation of the protein α-synuclein (α-syn) into spherical cytoplasmic inclusions, termed Lewy bodies, but are also observed in neuronal processes as Lewy neurites (LNs) (3).α-Syn is thought to play a central role in the pathobiology of Lewy body disease. Single-point mutations and genetic modifications affecting α-syn expression—through duplications, triplications, or polymorphisms in its promoter—have been linked to both idiopathic and familial forms of Lewy body disease (4–6). Nevertheless, neuropathological studies utilizing pan–α-syn antibodies, recognizing both physiological and pathological forms of the protein, do not consistently report a relationship between the load of Lewy body pathology and clinical disease severity (2). To reconcile the apparent importance of α-syn in Lewy body disease with the difficulty relating Lewy body burdens in the brain to phenotypic severity, continued research has focused on the identification of particularly disease-relevant forms of α-syn. α-Syn undergoes various posttranslational modifications (PTMs)—including acetylation, nitration, ubiquitination, and glycosylation and phosphorylation at serine 129 (pS129)—increases from ∼4% under physiological conditions to 90% in Lewy body disease, suggesting it is associated with the disease state (7–9).Previous studies have reported that pS129 enhances intracellular aggregate formation in SH-SY5Y cells (10), and mediates cell death through activation of the unfolded protein response pathway (11). Furthermore, studies in rodent models have suggested that pS129 exacerbates the rate of pathological protein aggregation and deposition, with subsequent negative effects on neuronal functioning (12). However, these studies are counterbalanced by others reporting a potentially neuroprotective function of phosphorylation in animal models (13, 14) and cellular model systems (15). Additionally, studies have reported neutral findings regarding pS129 modification as neither enhancing nor diminishing cellular toxicity and α-syn aggregation (16, 17). Despite the uncertain pathogenic role of pS129 in Lewy body disease, antibodies against pS129 are widely used, based on the putative view that they label a species of α-syn that is particularly disease-relevant. These studies often employ pS129–α-syn as a marker of the abundance of protein inclusions to stage disease severity and evaluate the relationship between its abundance and important clinical or pathological variables, such as disease duration, phenotypic severity, or cell loss (18). Such studies typically identify that pS129 abundance throughout the brain correlates with disease severity (19–21), though it remains uncertain whether phosphorylation precedes protein aggregation or occurs secondarily to deposition of nonphosphorylated α-syn, and whether pS129 is a key driver of pathogenicity or simply a useful marker of a neurodegenerative process (22, 23). Therefore, although there is a substantial literature on pS129 in Lewy body disease, there is continued controversy regarding its potential contribution to disease states, with numerous studies reporting discordant findings. Despite contradictory findings regarding the disease-relevance of pS129, it is widely viewed as a particularly disease-associated modification, thus necessitating further research to address its importance for Lewy body disease.To address the key questions regarding the pathogenic relevance of pS129–α-syn, the present study aimed to undertake a comprehensive and multidisciplinary project to address this important and pressing question. The key aim of the study was to better understand the role of pS129 in the natural history of Lewy body disease, by determining when pS129 occurs in the development of α-syn aggregates and how it affects the aggregation-propensity and cytotoxicity of α-syn